1. We have bred a strain of pigs with an inherited condition of hypocalcaemic rickets, transmitted by an autosomal-recessive mechanism.

2. Homozygous (affected) piglets grew at half the rate of their heterozygous (clinically normal) littermates, and developed profound hypocalcaemia with severe secondary hyperparathyroidism and hypophosphataemia by 8 weeks of age.

3. In the hypocalcaemic piglets, plasma 1,25-dihydroxyvitamin D levels were low or undetectable, and 24,25-dihydroxyvitamin D3 levels were also reduced despite 25-hydroxyvitamin D3 levels being 2-fold higher.

4. There was no detectable 25-hydroxyvitamin D3-1- or -24-hydroxylase enzyme activity in renal homogenates prepared from affected animals.

5. Plasma and intestinal calcium-binding protein levels were reduced in the hypocalcaemic piglets.

6. Sucrose density gradient analysis of intestinal cytosol, prepared in high-salt buffer, revealed the presence of a similar amount of a specific <4.2S 1,25-dihydroxyvitamin D3 binder in both groups of piglets.

7. Administration of pharmacological doses of vitamin D3 to affected animals reversed the hypocalcaemia.

8. We conclude that this strain of pigs has vitamin D-dependent rickets type I.

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